Role of Transient Receptor Potetial Canonical Channels in Glioma Cell Biology

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DESCRIPTION (provided by applicant): Malignant gliomas are thought to be glial-dervied and present a huge clincial challenge as the median survival is under 1 year. Characteristically, they proliferate and extensively invade throughout the brain parenchyma. Other studies have shown that ion channels are involved in the proliferation and migration of glioma cells and recently the transient receptor potential canonical (TRPC) channel family has been implicated in other cell types to facilitate proliferation. Therefore, the overall goal of this study is to understand the role transient receptor potential canonical channels play in glioma cell biology. Specifically, the first aim is to characterize TRPC channels in glioma cells by expression and electrophysiological profile. To accomplish the first aim, a combination of molecular and electrophysiological techniques will be utilized. The second aim is to address the role TRPC channels play in glioma cell proliferation. To address the second aim, a variety of cellular assays will be utilized along with imaging techniques to follow the cell cycle in the context of TRPC activity. The third aim investigates how glioma cells utilize TRPC channels in their migration and proliferation along blood vessels. The third aim will employ electrophysiological technique, confocal time-lapse microscopy, and in vivo models systems. PUBLIC HEALTH RELEVANCE: Since malignant gliomas proliferate and invade throughout the brain, the prognosis for patients diagnosed is extremely poor. Studies that further investigate the mechanisms gliomas utilize to enhance proliferation and invade throughout the brain may lend new insight into clinical treatment possibilities. Therefore, scientists, clinicians, and patients will benefit from an increased knowledge of these mechanisms.